Dehydroepiandrosterone (DHEA)
Dehydroepiandrosterone (DHEA)
Dehydroepiandrosterone (DHEA) is one of the androgens secreted by the adrenal cortex. An androgen is a hormone that stimulates masculine characteristics and is present in both males and females. The adrenal glands are small structures located at the tops of the kidneys. The adrenal medulla is the central portion of the adrenal gland and the adrenal cortex is the outer portion. The adrenal glands produce hormones that are involved in metabolism and stress reactions. These hormones are all produced from cholesterol. Three types of hormones are synthesized by the adrenal glands, glucocorticoids, mineralocorticoids, and sex hormone precursors. DHEA is one of the sex hormone precursors, which means it is eventually converted into the male sex hormone testosterone.
DHEA, along with its derivative dehydroepiandrosterone sulfate (DHEAS) are the most abundant steroids produced by the adrenal glands. Despite the high concentrations of DHEA in both the blood and the brain, no receptors have been found for the hormone and scientists have not determined its function in the body. The only scientifically proven fate of DHEA in the body is that it is eventually converted into the sex hormones. Many scientists have reported numerous beneficial effects of DHEA on the body. This hormone is marketed as a “wonder drug” that can be used to boost immune function, metabolism, endocrine function, as well as neurological functions. These claims are the results of recent studies involving DHEA supplementation and are quite preliminary. It is unknown whether these effects are directly due to the DHEA, or if they are the result of one of the metabolites of the hormone. In other words, the action of DHEA in the body is unknown.
DHEA as a neurosteroid
DHEA is different from other sex hormone precursors in that it is also a neurosteroid. A neurosteroid is a steroid that accumulates in the nervous system independently of its production in the endocrine glands. This means that DHEA found in the nervous system was not produced by the adrenal glands. DHEA has been found in the brains of humans, rodents, rabbits, monkeys, and dogs in relatively high concentrations. Studies suggest that the hormone acts directly on the brain. Although the hormone itself has been found in the adult brain, the enzyme needed for its production is only found in the brains of fetuses.
Because the enzyme needed for its production is found only in the brains of fetuses, it is thought that the hormone is somehow related to the organization and development of the brain. When DHEA is added to cultures of developing neurons from the brains of mouse embryos, it causes morphological changes such as increasing axon length. These studies suggest that certain developmental neurological disorders may actually be the result of lower than normal concentrations of DHEA in the fetal brain.
Actions of DHEA
The level of DHEA in the blood declines with age and also during times of stress or illness. Concentrations of this hormone in humans peak at about age 20, after which they steadily decline. By the time a person is 80 years old, their DHEA levels are only about 20% of what they were at their peak. The level of DHEA also declines with age in the brain. It has been suggested that this decline may play a role in some age-related illnesses. DHEA has been shown to
KEY TERMS
Anabolic steroid— Any of a group of synthetic steroid hormones sometimes abused by athletes in training to temporarily increase the size of their muscles.
Antioxicant— Any substance that prevents oxidation from occurring.
Atrophy— Decreasing in size or wasting away of a body part or tissue.
Autoimmune— Misdirected immune response in which lymphocytes mount an attack against normal body cells.
Endocrine system— A system of glands and other structures that secrete hormones to regulate certain body functions such as growth and development of sex characteristics.
Enzyme— Biological molecule, usually a protein, which promotes a biochemical reaction but is not consumed by the reaction.
Exogenous— Produced by factors outside the organism or system.
Interleukin— One of a variety of communication signals that drive immune responses.
Lupus— An autoimmune disease characterized by skin lesions.
Metabolite— A product of the controlled, enzyme-mediated chemical reactions by which cells acquire and use energy.
Morphology— Dealing with the form and structure of organisms.
Oxidation— Loss of electrons by a compound during a certain type of chemical reaction called a redox reaction.
Retrovirus— A type of virus that inserts its genetic material into the chromosomes of the cells it infects.
Seminiferous tubules— Tubes lining the testes which produce sperm.
Steroids— A group of organic compounds that belong to the lipid family and that include many important biochemical compounds including the sex hormones, certain vitamins, and cholesterol.
Testes— Male gonads, primary reproductive organs in which male gametes and sex hormones are produced.
act as an antioxidant, to enhance memory, and also to serve as a neuroprotector. Certain age-related diseases of the central nervous system, such as Alzheimer disease, are thought to be a result of oxidative stress in the brain. Because DHEA has been shown to demonstrate antioxidant properties in the brain, it has been hypothesized that it can be used to treat these age-related disorders. Although its action in these cases is still unclear, it is thought that it acts by protecting regions of the hippocampus from oxidative stress. It may also work by affecting the production of interleukin-6 (IL-6), which is believed to play a role in the progression of these diseases.
DHEA and DHEAS have been found to be useful in the treatment of certain autoimmune diseases. In one study, when mice were treated with DHEA at a young age, the onset of autoimmune disease was delayed and the mice lived longer. Once the mice had already shown signs of the disease, however, the hormone had no effect on disease progression. Another study demonstrated that DHEA supplementation helped reduce some of the effects of a retrovirus infection that caused acquired immune-deficiency syndrome (AIDS) in mice, such as vitamin E loss and lipid oxidation. DHEA boosted immune function and increased vitamin E levels in healthy mice as well. DHEA and DHEAS were also found to boost immune function in humans afflicted with Cushing’s syndrome and to delay the onset of lupus in mice.
It has also been suggested that DHEA is involved in stimulating bone mineral content and density. In rats, DHEA supplementation increased both lumbar spine and total body bone mineral density. This implies DHEA could be used to treat bone loss in aging patients or those suffering from certain diseases. Patients suffering from anorexia nervosa demonstrate severe bone loss as a side effect of this disease. DHEA levels in these patients are much lower than normal. DHEA supplementation in anorexic patients not only increased their bone mineral density, but also resulted in the resumption of menstrual cycles in many cases. Systemic lupus erythematosus patients also demonstrate severe bone loss. Preliminary clinical trials of DHEA supplements in these patients have suggested that this hormone could be used to treat bone loss in lupus sufferers as well.
There have been countless other claims of the benefits of DHEA in the body. DHEA may lower serum cholesterol levels. It may also protect against bacterial infections. DHEA has been found to decrease allergic responses in mice. Research is being conducted regarding the role of DHEA as a possible treatment for tuberculosis. This hormone has also been found to decrease anxiety in rats. The list of theories and proposals for the actions of DHEA on the body and the brain goes on and on.
Marketing
DHEA is currently available as a nutritional supplement. The Food and Drug Administration (FDA) has not approved its use for specific disorders. Because it is classified as a supplement, it can be purchased without a prescription. Since DHEA is a precursor to the production of testosterone, it could be considered an exogenous androgenic or anabolic steroid. Use of these steroids to enhance performance is banned from sports organizations and the military. At low doses, DHEA has a minimal effect on urine testosterone levels (the test used to screen for use of these drugs); however, at high doses this hormone would result in a “positive” test.
Side effects
The majority of the available research investigates the benefits of DHEA supplementation, but few studies discuss the possible adverse side effects associated with this hormone. One study found that prolonged DHEA treatment in rats induced liver tumors, especially in females. In male rats, sustained delivery DHEA and DHEAS treatments caused atrophy of the seminiferous tubules and testes. The application of the studies on the benefits of DHEA is also limited. Much research has been conducted on rats and mice, but few clinical trials on humans have actually been performed. More research is needed on the toxicity and morphological effects of DHEA and DHEAS, as well as on its specific action on humans, before its widespread use.
Resources
BOOKS
Solomon, Eldra Pearl. Biology. Orlando: Saunders College Publishing, 1999.
Starr, Cecie. Biology—Concepts and Applications. Belmont, CA: Wadsworth Publishing Company, 1997.
PERIODICALS
Gordon, C. “Changes in Bone Turnover Markers and Menstrual Function after Short-Term DHEA in Young Women with Anorexia Nervosa.” Journal of Bone and Mineral Research 14, no. 1 (1999).
Prasad, A. “Dehydroepiandrosterone DecreasesBehavioral Dispair in High—but not Low—Anxiety Rats.” Physiology & Behavior 62, no. 5 (1997).
OTHER
University of Maryland Medical Center “Dehydroepiandrosterone (DHEA)” <http://www.umm.edu/altmed/ConsSupplements/DehydroepiandrosteroneDHEAcs.html> (accessed November 18, 2006).
The Why Files: Science behind the News. “One Pill Makes You Smaller: A Workhorse Hormone?” <http://whyfiles.org/051fat_fixes/dhea.html> (accessed November 16, 2006).
Jennifer McGrath